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ORIGINAL ARTICLE
Physical activity in patients with idiopathic pulmonary fibrosis MASAYUKI NAKAYAMA,1 MASASHI BANDO,1 KOJI ARAKI,2 TOSHIE SEKINE,2 FUMIO KUROSAKI,1 TETSURO SAWATA,1 SHOKO NAKAZAWA,1 NAOKO MATO,1 HIDEAKI YAMASAWA1 AND YUKIHIKO SUGIYAMA1 1
Division of Pulmonary Medicine, Department of Medicine and 2Department of Rehabilitation, Jichi Medical University, Shimotsuke, Japan
ABSTRACT Background and objective: Physical activity is an important parameter in patients with chronic obstructive pulmonary disease, but has not been studied in detail in patients with interstitial lung disease. This study aimed to evaluate physical activity in patients with idiopathic pulmonary fibrosis (IPF). Methods: Physical activity was monitored in 31 stable IPF patients using an accelerometer for 1 month. The following factors reflecting physical activity were measured: the number of steps, walking distance, the time spent at magnitude of movement (MM) 1–6, physical activity-related energy expenditure (PAEE) and total energy expenditure.We also measured the following clinical parameters: the modified Medical Research Council (MRC) scale, Krebs von den Lungen-6 (KL-6), pulmonary function parameters, 6-min walk test (6MWT) results and high-resolution computed tomography (HRCT) findings of the chest. We determined the relationship between these parameters and physical activity. Results: We recorded 24 days of physical activity data. The time spent at MM < 1 was more than 10 h per day, whereas that at MM > 1 was approximately 1 h per day. The modified MRC scale, serum KL-6 levels, 6MWT distance, and the extent of honeycomb and reticular abnormality on HRCT were associated with several facets of physical activity. In particular, lower KL-6 levels were correlated with higher physical activity based on the number of steps, walking distance, the time spent at MM 1–4 and PAEE. Conclusions: The modified MRC scale, 6MWT distance, extent of fibrosis on HRCT and serum KL-6 levels are strongly associated with physical activity. Key words: accelerometer, idiopathic pulmonary fibrosis, Krebs von den Lungen-6, physical activity, 6-min walk test. Abbreviations: 6MWT, 6-min walk test; BNP, brain natriuretic peptide; COPD, chronic obstructive pulmonary disease; DLCO, difCorrespondence: Masayuki Nakayama, Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. E-mail: [email protected] Received 16 June 2014; invited to revise 11 August 2014; revised 7 November 2014; accepted 20 December 2014 (Associate Editor: Neil Eves). Article first published online: 27 February 2015 © 2015 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We evaluated physical activity in patients with IPF. The modified MRC scale, 6MWT distance, extent of honeycomb and reticular abnormality on HRCT scans of the chest, and serum KL-6 levels were strongly correlated with physical activity. Physical activity may be an important indicator in multifaceted evaluation of patients with IPF.
fusing capacity for carbon monoxide; fIIP, fibrotic idiopathic interstitial pneumonia; FVC, forced vital capacity; HRCT, highresolution computed tomography; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lungen-6; MET, metabolic equivalent; MRC, Medical Research Council; MM, magnitude of movement; PAEE, physical activityrelated energy expenditure; PAH, pulmonary arterial hypertension; SP-D, surfactant protein D; SpO2, oxygen saturation as measured by pulse oximetry.
INTRODUCTION Physical activity, as measured with an accelerometer, is an important parameter in patients with chronic obstructive pulmonary disease (COPD). Daily physical activity has implications for disease progression, quality of life, risk of COPD-related hospital admission and mortality.1–3 However, physical activity in patients with interstitial lung disease (ILD) has not been well examined. In a routine medical examination, patients with ILD are evaluated by clinical parameters, such as the pulmonary function test, 6-min walk test (6MWT) and serum ILD biomarkers, as well as with high-resolution computed tomography (HRCT) of the chest. However, the relationships between these clinical parameters or radiological assessment and physical activity have not been clarified. This study aimed to monitor physical activity in patients with ILD, especially those with idiopathic pulmonary fibrosis (IPF), using an accelerometer, and to examine the relationships between various clinical or radiological assessment and physical activity. Respirology (2015) 20, 640–646 doi: 10.1111/resp.12500
Physical activity in IPF
METHODS Subjects Thirty-one patients who had been diagnosed with IPF were recruited in Jichi Medical University Hospital between January 2012 and December 2013. All of the IPF patients were clinically diagnosed on the basis of an official statement in 2011.4 HRCT of the chest was independently reviewed by three pulmonologists (M.N., M.B. and Y.S.). The patients did not have any episodes of pneumonia or acute exacerbation for at least 1 year prior to the study. For treatment, N-acetyl cysteine was administered to eight patients, pirfenidone to three patients, prednisolone to two patients and long-term oxygen therapy to two patients. Subjects were excluded if they had at least one of the following criteria: (i) they had ILD other than IPF; (ii) they had comorbidities that were considered to affect their daily activities, including central nervous system diseases, cardiovascular diseases including pulmonary arterial hypertension (PAH), orthopaedic diseases and malignant diseases; (iii) they were complicated by emphysema in the upper lung field, which indicated combined pulmonary fibrosis and emphysema; and (iv) they were introduced to a pulmonary rehabilitation programme. The protocol was approved by the Ethics Committee in Jichi Medical University Hospital (A09-76). Patients provided written informed consent. Clinical assessment Clinical parameters of the patients with IPF, including their background (age, gender and body mass index), evaluation of the dyspnoea scale or quality of life (modified Medical Research Council (MRC) scale and COPD assessment test), blood test results, such as serum ILD biomarkers (Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D)) and brain natriuretic peptide (BNP), pulmonary function parameters and 6MWT results, were extracted from their medical records. Measurement of blood samples Serum KL-6 and SP-D levels were measured with commercially available enzyme-linked immunosorbent assay kits (Eidia, Tokyo, Japan). Plasma BNP levels were also measured commercially. HRCT assessment We assessed the presence of honeycomb and reticular abnormalities independently in the lower zones of the lungs, defined as the level of the inferior pulmonary vein. We determined the extent of each abnormality by visually estimating the percentage (to the nearest 10%). Assessments by the three pulmonologists were averaged. Pulmonary function test Spirometry was performed, and we investigated the lung volume compartment and pulmonary diffusing © 2015 Asian Pacific Society of Respirology
641 capacity, according to standard criteria.5–7 The results (forced vital capacity (FVC), forced expiratory volume in 1 s, total lung capacity and diffusing capacity for carbon monoxide (DLCO)) were reported as a percentage of the predicted values. The rate of deterioration of FVC and DLCO in 1 year was examined before and after monitoring physical activity.
6MWT The 6MWT was conducted without supplemental oxygen in accordance with American Thoracic Society statement,8 with the modification that heart rate and oxygen saturation, as measured by pulse oximetry (SpO2), were recorded at the start and end of each minute of the test. Physical activity monitor A uniaxial physical activity monitor, Lifecorder GS (Suzuken Co., Ltd., Nagoya, Aichi, Japan), was used. This device is small and lightweight (72 × 42 × 29 mm, 45 g). This monitor categorizes the magnitude of movement (MM), which represents exercise intensity during each 2-min interval, as a scale of MM 1 (minimal) to MM 9 (maximal). The MMs are subsequently converted by an algorithm to calculate energy expenditure (kcal). MM levels closely approximated the metabolic equivalents (MET) of the activities being performed.9 MM 1 was equivalent to walking slowly (approximately 1.3 MET) while MM 9 was equivalent to running fast (approximately 9.1 MET). Measurement of physical activity and data analysis The subjects were instructed to put the monitor on their waist belts every day for 1 month under freeliving conditions. Several factors that affected physical activity data were excluded. First, subjects become inactive in a cold winter or hot summer,10 or on rainy or snowy days.11 Therefore, we avoided putting the monitor on subjects in these seasons (January, July, August and December) and excluded data obtained on rainy or snowy days during the monitoring period. Second, some subjects forgot to put the monitor on. When analysing data that were obtained from physical activity monitors, we found it difficult to distinguish whether subjects had put the monitor on without walking or had forgotten to put it on. However, this monitor can sense slight trunk movement without walking, which is too small to be measured as physical activity (MM < 1). Therefore, we could distinguish this difference by investigating the data in detail. We then extracted data for analysis only on days when the subjects put the monitor on for more than 10 h per day and calculated the mean data per day in each subject. The following seven factors were evaluated: (i) the number of steps (steps/day), (ii) walking distance (m/day), (iii) the time spent at light intensity (MM 1–2) (min/day), (iv) the time spent at light-tomoderate intensity (MM 3–4) (min/day), (v) the time spent at moderate intensity (MM 5–6) (min/day), (vi) Respirology (2015) 20, 640–646
642 Table 1
M Nakayama et al. Clinical characteristics in 31 patients with IPF
Age (y) Gender BMI (kg/m2) Past smoking history (pack-year) Modified MRC scale (0/1/2) KL-6 (U/mL) SP-D (ng/mL) BNP (pg/mL) FVC, % pred TLC, %pred DLCO, %pred SpO2 at rest (%) Heart rate at rest (/min) 6MWT distance (m) Lowest SpO2 in the 6MWT (%)
68.3 ± 6.3 M/F 22/9 24.2 ± 2.9 26.3 ± 26.4 17/12/2 922 ± 465 222 ± 119 23.3 ± 20.1 88.7 ± 20.5 84.4 ± 16.8 78.8 ± 21.8 96.9 ± 1.3 86.2 ± 15.9 436 ± 82.0 90.0 ± 3.3
Data are expressed as means ± standard deviations. 6MWT, 6-min walk test; %pred, per cent of the predicted; BMI, body mass index; BNP, brain natriuretic peptide; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lungen-6; MRC, Medical Research Council; SP-D, surfactant protein D; SpO2, oxygen saturation as measured by pulse oximetry; TLC, total lung capacity.
physical activity-related energy expenditure (PAEE), which was calculated from the sum of MM 1–9 (kcal/ day), and (vii) total energy expenditure, which was the sum of PAEE, basal metabolism and energy expenditure calculated as MM < 1 (kcal/day). We evaluated the relationship between physical activity as measured with the accelerometer and clinical or radiological assessment in patients with IPF.
Statistical analyses Data are expressed as means with standard deviations. The relationships between physical activity and clinical or radiological assessment were analysed using univariate and multivariate analyses. Analysis of variance or simple regression was used with univariate analysis. Analysis of covariance was used with multivariate analysis. The covariates adjusted in this study included age (years), gender and body mass index (kg/m2). We did not perform adjustment for multiplicity. All statistical analyses were performed using the SAS software program (version 9.1.3, SAS Institute, Cary, NC, USA). Significance was set at P < 0.05.
RESULTS All of the subjects remained in a clinically stable condition throughout the monitoring period. They were all retired or housewives. Their clinical characteristics are shown in Table 1. Their mean pulmonary function parameters were approximately within the normal range and exercise tolerance was maintained. Data measured using the Lifecorder are shown in Table 2. We successfully recorded 24 days of physical activity. According to exercise intensity, the time spent Respirology (2015) 20, 640–646
Table 2 Data extracted from the Lifecorder in 31 patients with IPF Analysed days (d) Steps (steps/d) Walking distance (m/d) MM < 1 (min/d) MM 1–2 (min/d) MM 3–4 (min/d) MM 5–6 (min/d) MM 7–8 (min/d) PAEE (kcal/d) TEE (kcal/d)
24.5 ± 7.8 6520 ± 3340 4488 ± 2307 611.2 ± 88.9 43.4 ± 19.7 20.6 ± 15.1 5.9 ± 10.5 0.7 ± 2.2 167.7 ± 98.4 1804 ± 272
Data are expressed as means ± standard deviations. IPF, idiopathic pulmonary fibrosis; MM, magnitude of movement; PAEE, physical activity-related energy expenditure; TEE, total energy expenditure.
at MM < 1 was more than 10 h per day, whereas that spent at MM > 1 was approximately 1 h per day, which indicated that the subjects were not walking more than 90% of their total activity. Furthermore, the time spent at MM > 4, which was equivalent to running, was only 6 min per day. The time spent at high intensity (MM 7–9) was too short to evaluate. The relationships between physical activity and clinical or radiological assessment are shown in Tables 3–7. The modified MRC scale, serum KL-6 levels, 6MWT results and the extent of fibrosis (i.e. honeycomb and reticular abnormality) on HRCT were associated with at least one factor of physical activity. In particular, the lower the KL-6 level and the longer the 6MWT distance were, the higher physical activity was regarding several factors (steps, walking distance, the time spent at MM 1–2 and PAEE). Furthermore, KL-6 levels were associated with the time spent at MM 3–4. The lowest SpO2 during 6MWT was only associated with the time spent at MM 5–6. The extent of fibrosis was associated with total energy expenditure and the time spent at MM 1–2. In contrast, COPD assessment test results, serum SP-D levels, plasma BNP levels and all pulmonary function parameters were not associated with any factors of physical activity (data not shown).
DISCUSSION In the present study, we measured physical activity in 31 patients with stable IPF using a compact accelerometer. We found that the modified MRC scale, 6MWT distance, the extent of fibrosis on HRCT and especially serum KL-6 levels were associated with several factors reflecting physical activity. We only studied patients with IPF because heterogeneous characteristics in ILD may affect their physical activity. Furthermore, comorbidities reduce physical activity in patients with COPD.12 Therefore, we excluded patients who had comorbidities (described in the Methods section) in the present study. We did not perform right heart catheterization in any patients. We performed echocardiography in © 2015 Asian Pacific Society of Respirology
643
Physical activity in IPF Table 3 Relationships between clinical parameters and physical activity (steps per day) Univariate Variable
Type
KL-6 (U/mL)
Disc.
6MWT distance (m)
Cont. Disc.
Category Q1: Q2: Q3: Q4:
1211
Q1: Q2: Q3: Q4:
480
Cont.
N
Mean
SD
Estimate†
7 8 8 8 — 7 8 7 9 —
9239.44 6187.44 5848.03 5145.42 — 4492.05 5472.05 8074.20 7820.35 —
4010.58 3273.70 1486.74 3302.74 — 3356.07 2876.19 3217.16 3111.48 —
Reference −3052.00 −3391.41 −4094.02 −3.09 Reference 980.00 3582.15 3328.30 17.32
Multivariate
P-value
0.07
ORIGINAL ARTICLE
Physical activity in patients with idiopathic pulmonary fibrosis MASAYUKI NAKAYAMA,1 MASASHI BANDO,1 KOJI ARAKI,2 TOSHIE SEKINE,2 FUMIO KUROSAKI,1 TETSURO SAWATA,1 SHOKO NAKAZAWA,1 NAOKO MATO,1 HIDEAKI YAMASAWA1 AND YUKIHIKO SUGIYAMA1 1
Division of Pulmonary Medicine, Department of Medicine and 2Department of Rehabilitation, Jichi Medical University, Shimotsuke, Japan
ABSTRACT Background and objective: Physical activity is an important parameter in patients with chronic obstructive pulmonary disease, but has not been studied in detail in patients with interstitial lung disease. This study aimed to evaluate physical activity in patients with idiopathic pulmonary fibrosis (IPF). Methods: Physical activity was monitored in 31 stable IPF patients using an accelerometer for 1 month. The following factors reflecting physical activity were measured: the number of steps, walking distance, the time spent at magnitude of movement (MM) 1–6, physical activity-related energy expenditure (PAEE) and total energy expenditure.We also measured the following clinical parameters: the modified Medical Research Council (MRC) scale, Krebs von den Lungen-6 (KL-6), pulmonary function parameters, 6-min walk test (6MWT) results and high-resolution computed tomography (HRCT) findings of the chest. We determined the relationship between these parameters and physical activity. Results: We recorded 24 days of physical activity data. The time spent at MM < 1 was more than 10 h per day, whereas that at MM > 1 was approximately 1 h per day. The modified MRC scale, serum KL-6 levels, 6MWT distance, and the extent of honeycomb and reticular abnormality on HRCT were associated with several facets of physical activity. In particular, lower KL-6 levels were correlated with higher physical activity based on the number of steps, walking distance, the time spent at MM 1–4 and PAEE. Conclusions: The modified MRC scale, 6MWT distance, extent of fibrosis on HRCT and serum KL-6 levels are strongly associated with physical activity. Key words: accelerometer, idiopathic pulmonary fibrosis, Krebs von den Lungen-6, physical activity, 6-min walk test. Abbreviations: 6MWT, 6-min walk test; BNP, brain natriuretic peptide; COPD, chronic obstructive pulmonary disease; DLCO, difCorrespondence: Masayuki Nakayama, Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. E-mail: [email protected] Received 16 June 2014; invited to revise 11 August 2014; revised 7 November 2014; accepted 20 December 2014 (Associate Editor: Neil Eves). Article first published online: 27 February 2015 © 2015 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We evaluated physical activity in patients with IPF. The modified MRC scale, 6MWT distance, extent of honeycomb and reticular abnormality on HRCT scans of the chest, and serum KL-6 levels were strongly correlated with physical activity. Physical activity may be an important indicator in multifaceted evaluation of patients with IPF.
fusing capacity for carbon monoxide; fIIP, fibrotic idiopathic interstitial pneumonia; FVC, forced vital capacity; HRCT, highresolution computed tomography; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lungen-6; MET, metabolic equivalent; MRC, Medical Research Council; MM, magnitude of movement; PAEE, physical activityrelated energy expenditure; PAH, pulmonary arterial hypertension; SP-D, surfactant protein D; SpO2, oxygen saturation as measured by pulse oximetry.
INTRODUCTION Physical activity, as measured with an accelerometer, is an important parameter in patients with chronic obstructive pulmonary disease (COPD). Daily physical activity has implications for disease progression, quality of life, risk of COPD-related hospital admission and mortality.1–3 However, physical activity in patients with interstitial lung disease (ILD) has not been well examined. In a routine medical examination, patients with ILD are evaluated by clinical parameters, such as the pulmonary function test, 6-min walk test (6MWT) and serum ILD biomarkers, as well as with high-resolution computed tomography (HRCT) of the chest. However, the relationships between these clinical parameters or radiological assessment and physical activity have not been clarified. This study aimed to monitor physical activity in patients with ILD, especially those with idiopathic pulmonary fibrosis (IPF), using an accelerometer, and to examine the relationships between various clinical or radiological assessment and physical activity. Respirology (2015) 20, 640–646 doi: 10.1111/resp.12500
Physical activity in IPF
METHODS Subjects Thirty-one patients who had been diagnosed with IPF were recruited in Jichi Medical University Hospital between January 2012 and December 2013. All of the IPF patients were clinically diagnosed on the basis of an official statement in 2011.4 HRCT of the chest was independently reviewed by three pulmonologists (M.N., M.B. and Y.S.). The patients did not have any episodes of pneumonia or acute exacerbation for at least 1 year prior to the study. For treatment, N-acetyl cysteine was administered to eight patients, pirfenidone to three patients, prednisolone to two patients and long-term oxygen therapy to two patients. Subjects were excluded if they had at least one of the following criteria: (i) they had ILD other than IPF; (ii) they had comorbidities that were considered to affect their daily activities, including central nervous system diseases, cardiovascular diseases including pulmonary arterial hypertension (PAH), orthopaedic diseases and malignant diseases; (iii) they were complicated by emphysema in the upper lung field, which indicated combined pulmonary fibrosis and emphysema; and (iv) they were introduced to a pulmonary rehabilitation programme. The protocol was approved by the Ethics Committee in Jichi Medical University Hospital (A09-76). Patients provided written informed consent. Clinical assessment Clinical parameters of the patients with IPF, including their background (age, gender and body mass index), evaluation of the dyspnoea scale or quality of life (modified Medical Research Council (MRC) scale and COPD assessment test), blood test results, such as serum ILD biomarkers (Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D)) and brain natriuretic peptide (BNP), pulmonary function parameters and 6MWT results, were extracted from their medical records. Measurement of blood samples Serum KL-6 and SP-D levels were measured with commercially available enzyme-linked immunosorbent assay kits (Eidia, Tokyo, Japan). Plasma BNP levels were also measured commercially. HRCT assessment We assessed the presence of honeycomb and reticular abnormalities independently in the lower zones of the lungs, defined as the level of the inferior pulmonary vein. We determined the extent of each abnormality by visually estimating the percentage (to the nearest 10%). Assessments by the three pulmonologists were averaged. Pulmonary function test Spirometry was performed, and we investigated the lung volume compartment and pulmonary diffusing © 2015 Asian Pacific Society of Respirology
641 capacity, according to standard criteria.5–7 The results (forced vital capacity (FVC), forced expiratory volume in 1 s, total lung capacity and diffusing capacity for carbon monoxide (DLCO)) were reported as a percentage of the predicted values. The rate of deterioration of FVC and DLCO in 1 year was examined before and after monitoring physical activity.
6MWT The 6MWT was conducted without supplemental oxygen in accordance with American Thoracic Society statement,8 with the modification that heart rate and oxygen saturation, as measured by pulse oximetry (SpO2), were recorded at the start and end of each minute of the test. Physical activity monitor A uniaxial physical activity monitor, Lifecorder GS (Suzuken Co., Ltd., Nagoya, Aichi, Japan), was used. This device is small and lightweight (72 × 42 × 29 mm, 45 g). This monitor categorizes the magnitude of movement (MM), which represents exercise intensity during each 2-min interval, as a scale of MM 1 (minimal) to MM 9 (maximal). The MMs are subsequently converted by an algorithm to calculate energy expenditure (kcal). MM levels closely approximated the metabolic equivalents (MET) of the activities being performed.9 MM 1 was equivalent to walking slowly (approximately 1.3 MET) while MM 9 was equivalent to running fast (approximately 9.1 MET). Measurement of physical activity and data analysis The subjects were instructed to put the monitor on their waist belts every day for 1 month under freeliving conditions. Several factors that affected physical activity data were excluded. First, subjects become inactive in a cold winter or hot summer,10 or on rainy or snowy days.11 Therefore, we avoided putting the monitor on subjects in these seasons (January, July, August and December) and excluded data obtained on rainy or snowy days during the monitoring period. Second, some subjects forgot to put the monitor on. When analysing data that were obtained from physical activity monitors, we found it difficult to distinguish whether subjects had put the monitor on without walking or had forgotten to put it on. However, this monitor can sense slight trunk movement without walking, which is too small to be measured as physical activity (MM < 1). Therefore, we could distinguish this difference by investigating the data in detail. We then extracted data for analysis only on days when the subjects put the monitor on for more than 10 h per day and calculated the mean data per day in each subject. The following seven factors were evaluated: (i) the number of steps (steps/day), (ii) walking distance (m/day), (iii) the time spent at light intensity (MM 1–2) (min/day), (iv) the time spent at light-tomoderate intensity (MM 3–4) (min/day), (v) the time spent at moderate intensity (MM 5–6) (min/day), (vi) Respirology (2015) 20, 640–646
642 Table 1
M Nakayama et al. Clinical characteristics in 31 patients with IPF
Age (y) Gender BMI (kg/m2) Past smoking history (pack-year) Modified MRC scale (0/1/2) KL-6 (U/mL) SP-D (ng/mL) BNP (pg/mL) FVC, % pred TLC, %pred DLCO, %pred SpO2 at rest (%) Heart rate at rest (/min) 6MWT distance (m) Lowest SpO2 in the 6MWT (%)
68.3 ± 6.3 M/F 22/9 24.2 ± 2.9 26.3 ± 26.4 17/12/2 922 ± 465 222 ± 119 23.3 ± 20.1 88.7 ± 20.5 84.4 ± 16.8 78.8 ± 21.8 96.9 ± 1.3 86.2 ± 15.9 436 ± 82.0 90.0 ± 3.3
Data are expressed as means ± standard deviations. 6MWT, 6-min walk test; %pred, per cent of the predicted; BMI, body mass index; BNP, brain natriuretic peptide; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; KL-6, Krebs von den Lungen-6; MRC, Medical Research Council; SP-D, surfactant protein D; SpO2, oxygen saturation as measured by pulse oximetry; TLC, total lung capacity.
physical activity-related energy expenditure (PAEE), which was calculated from the sum of MM 1–9 (kcal/ day), and (vii) total energy expenditure, which was the sum of PAEE, basal metabolism and energy expenditure calculated as MM < 1 (kcal/day). We evaluated the relationship between physical activity as measured with the accelerometer and clinical or radiological assessment in patients with IPF.
Statistical analyses Data are expressed as means with standard deviations. The relationships between physical activity and clinical or radiological assessment were analysed using univariate and multivariate analyses. Analysis of variance or simple regression was used with univariate analysis. Analysis of covariance was used with multivariate analysis. The covariates adjusted in this study included age (years), gender and body mass index (kg/m2). We did not perform adjustment for multiplicity. All statistical analyses were performed using the SAS software program (version 9.1.3, SAS Institute, Cary, NC, USA). Significance was set at P < 0.05.
RESULTS All of the subjects remained in a clinically stable condition throughout the monitoring period. They were all retired or housewives. Their clinical characteristics are shown in Table 1. Their mean pulmonary function parameters were approximately within the normal range and exercise tolerance was maintained. Data measured using the Lifecorder are shown in Table 2. We successfully recorded 24 days of physical activity. According to exercise intensity, the time spent Respirology (2015) 20, 640–646
Table 2 Data extracted from the Lifecorder in 31 patients with IPF Analysed days (d) Steps (steps/d) Walking distance (m/d) MM < 1 (min/d) MM 1–2 (min/d) MM 3–4 (min/d) MM 5–6 (min/d) MM 7–8 (min/d) PAEE (kcal/d) TEE (kcal/d)
24.5 ± 7.8 6520 ± 3340 4488 ± 2307 611.2 ± 88.9 43.4 ± 19.7 20.6 ± 15.1 5.9 ± 10.5 0.7 ± 2.2 167.7 ± 98.4 1804 ± 272
Data are expressed as means ± standard deviations. IPF, idiopathic pulmonary fibrosis; MM, magnitude of movement; PAEE, physical activity-related energy expenditure; TEE, total energy expenditure.
at MM < 1 was more than 10 h per day, whereas that spent at MM > 1 was approximately 1 h per day, which indicated that the subjects were not walking more than 90% of their total activity. Furthermore, the time spent at MM > 4, which was equivalent to running, was only 6 min per day. The time spent at high intensity (MM 7–9) was too short to evaluate. The relationships between physical activity and clinical or radiological assessment are shown in Tables 3–7. The modified MRC scale, serum KL-6 levels, 6MWT results and the extent of fibrosis (i.e. honeycomb and reticular abnormality) on HRCT were associated with at least one factor of physical activity. In particular, the lower the KL-6 level and the longer the 6MWT distance were, the higher physical activity was regarding several factors (steps, walking distance, the time spent at MM 1–2 and PAEE). Furthermore, KL-6 levels were associated with the time spent at MM 3–4. The lowest SpO2 during 6MWT was only associated with the time spent at MM 5–6. The extent of fibrosis was associated with total energy expenditure and the time spent at MM 1–2. In contrast, COPD assessment test results, serum SP-D levels, plasma BNP levels and all pulmonary function parameters were not associated with any factors of physical activity (data not shown).
DISCUSSION In the present study, we measured physical activity in 31 patients with stable IPF using a compact accelerometer. We found that the modified MRC scale, 6MWT distance, the extent of fibrosis on HRCT and especially serum KL-6 levels were associated with several factors reflecting physical activity. We only studied patients with IPF because heterogeneous characteristics in ILD may affect their physical activity. Furthermore, comorbidities reduce physical activity in patients with COPD.12 Therefore, we excluded patients who had comorbidities (described in the Methods section) in the present study. We did not perform right heart catheterization in any patients. We performed echocardiography in © 2015 Asian Pacific Society of Respirology
643
Physical activity in IPF Table 3 Relationships between clinical parameters and physical activity (steps per day) Univariate Variable
Type
KL-6 (U/mL)
Disc.
6MWT distance (m)
Cont. Disc.
Category Q1: Q2: Q3: Q4:
1211
Q1: Q2: Q3: Q4:
480
Cont.
N
Mean
SD
Estimate†
7 8 8 8 — 7 8 7 9 —
9239.44 6187.44 5848.03 5145.42 — 4492.05 5472.05 8074.20 7820.35 —
4010.58 3273.70 1486.74 3302.74 — 3356.07 2876.19 3217.16 3111.48 —
Reference −3052.00 −3391.41 −4094.02 −3.09 Reference 980.00 3582.15 3328.30 17.32
Multivariate
P-value
0.07
